Creutzfeldt-Jakob disease is a fatal, transmissible form of dementia. Because of its infectious nature, diagnosis of this disease is most important.
The infectious agent is referred to as an "unconventional" virus or prion. There is no specific immune response to the infectious particle in the brain, serum, or cerebrospinal fluid of patients with this disease. Therefore, the usual diagnosis is an antemortem diagnosis which must be made by biopsy of affected brain tissue. The closest known technology for accurately diagnosing Creutzfeldt-Jakob disease is by directly examining abnormal brain tissue, either by light microscopy of a brain biopsy, identifying the presence or absence of a protein PrP 27-30 in extracts of brain biopsy tissue, or by a combination of the above, post-mortem. Detection of scrapie-associated fibrils by negative-stain electron microscopy and of "prion" proteins by electrophoresis of extracts from brain tissue provide additional information that is useful for diagnosis.
While it is possible to biopsy a live brain, this procedure is undertaken only with great reluctance for obvious reasons having to do with the adverse effects coupled with little potential benefit to the patient. A biopsy of brain tissue is not performed until late in the course of the disease because of the inherent risks of the procedure. On the other hand, cerebrospinal fluid can be readily obtained from patients. Unfortunately for the purpose of diagnosis, scrapie-associated fibrils and prion proteins have not yet been detected in spinal fluid.
Progress over the last decade in protein separation and staining has allowed the detection of approximately 300 proteins in the cerebrospinal fluid. Hartman, in U.S. Pat. No. 4,654,313, describes a radioimmunoassay for the determination of brain antigens or protein such as S-100, which is responsible for some neurological disorders.
Searcy et al., in U.S. Pat. No. 3,201,202, disclose a method for microquantitation of proteins in cerebrospinal fluid, but there is no disclosure of the purpose for which such proteins are quantitated.
Whitaker, in U.S. Pat. No. 4,205,057, disclose a method for isolating and using cerebrospinal fluid myelin encephalitogenic protein fragments as a disease indicator in multiple sclerosis.
Galvez et al., in Neurology 29: 1610-1612 (1970), disclose that the concentrations of IgA, IgG, and C3 in spinal fluid was increased over that of controls, suggesting a passage of IgG and C3 from the blood into spinal fluid.
Olsson, in European Neurology 19: 85-90 (1980), writes that no special abnormalities were found in cerebrospinal fluid from patients with Creutzfeldt-Jakob disease concerning cells, total protein content, or the concentrations of albumin and IgG.
Chu et al., in Annals of Neurology 13 (4): 434-439 (1983), discloses that no oligoclonal immunoglobulin G bands were detected in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.